We propose to study prospectively whether the risk of Parkinson's disease (PD) is predicted by plasma levels of organochlorine pesticides, polychlorinated biphenyls (PCBs), and the antioxidant uric acid. The proposed investigation will take advantage of a unique population comprising over 35,000 Finnish men and women who provided blood samples in 1968-72 as part of a health examination survey, and have subsequently been followed for incidence of PD for over 20 years. Between the baseline survey and 1994, 201 new cases of PD have been confirmed in this population. Plasma levels of organochlorine insecticides, PCBs, and uric acid will be assessed among these cases and controls matched by age and gender. Specific hypotheses to be tested include: 1) That higher plasma levels of para, para-dichlorodiphenyl dichloroethene [p,p-DDE], the major metabolite of DDT, dieldrin, hexachlorobenzene (HCB), beta-hexachlorocyclohexane (HCH), heptachlor, heptachlor epoxide, trans-nonachlor, and oxychlordane are associated with increase risk of PD; 2) that higher plasma levels of PCBs (sum of all congeners) are associated with an increased risk of PD; and 3) that higher plasma levels of the antioxidant uric acid are associated with a decreased risk of PD, and exert a protective effect against the deleterious effects of DDE. The proposed investigation is unique and innovative as there are no previous data relating biomarkers of exposure to environmental contaminants and future risk of developing PD. The blood samples were collected at a time of high exposure to both organochlorine insecticides and PCBs as supported by the high mean plasma level of DDE and PCBs that we found in a pilot study. Finally, the long follow-up period will allow the investigation of long-term effects of exposure.